钾离子通道开放剂二氮嗪静脉注射对正常大鼠血糖及胰岛素敏感性的影响

Influence of intravenous Diazoxide treatment on plasma glucose and insulin sensitivity in normal rats

目的观察二氮嗪（DZ）对正常大鼠血糖及IS的影响。方法 SD大鼠22只随机分为正常对照（Con）组和DZ组,每组各11只。两组在空腹8～10 h后予颈静脉插管,Con组输注生理盐水6 h,DZ组从颈静脉注射DZ（30 mg/kg）后,输注生理盐水,作正常血糖高胰岛素钳夹试验,以葡萄糖输注率（GIR）评价IS。实验结束后,检测血糖和胰岛素,取骨骼肌肌肉组织,行RT-PCR检测葡萄糖转运蛋白4（GLUT4）、胰岛素受体（INSR）、胰岛素受体底物1（IRS1）及胰岛素受体底物2（IRS2）基因表达。结果（1）DZ组血糖水平较Con组增高[（6.78±0.86）vs（13.83±0.94）mmol/L,P〈0.01],胰岛素水平下降[（11.58±0.82）vs（9.84±0.86）μIU/ml,P〈0.01）];（2）DZ组GIR较Con组下降约55.6%（P〈0.01）;（3）DZ组肌肉组织GLUT4、INSR、IRS1、IRS2基因表达较Con组分别减少约17%、44%、15%及13%（P〈0.05或P〈0.01）。结论 DZ静脉输注可以导致正常大鼠血糖增高、胰岛素水平减少及IR。

Objective To investigate the influence of intravenous Diazoxide treatment on plasma glucose and insulin sesitivity in normal rats.Methods A total of 22 male Sprague-Dawley（SD）rats were randomly divided into Diazoxide-treatment group（DZ group,n=11）and control group（Con group,n=11）.Cannulation through jugular vein was done after fasting for 8～10 hours.Con group was infused with saline for 6 hours,and DZ group was injected with Diazoxide（30 mg/kg）intravenously then infused with saline.Glucose infusion rate（GIR）was measured by euglycemic hyperinsulinemic clamp to evaluate insulin sensitivity.Plasma glucose and insulin were tested after treatment.The gene expression of glucose transporter 4（GLUT4）,insulin receptor（IR）,insulin receptor substrate 1（IRS1）,and insulin receptor substrate 2（IRS2）in the skeletal muscle were determined by RT-PCR.Results（1）Plasma glucose value increased[（6.78±0.86）vs（13.83±0.94）mmol/L,P〈0.01],insulin level decreased[（11.58±0.82）vs（9.84±0.86）μIU/ml,P〈0.01]significantly in DZ group than in Con group.（2）GIR decreased 55.6%in DZ group than in Con group（P〈0.01）.（3） The mRNA levels of GLUT4,INSR,IRS1 and IRS2 were significantly decreased by about 17%,44%,15%and 13%in DZ group than in Con group（P〈0.01 or P〈0.05）.Conclusion Intravenous Diazoxide may increase glucose,decrease insulin,and cause insulin resistance.